Pseudomonas aeruginosa is responsible for approximately 10% of the hospital-acquired infections in the U.S., and causes a chronic, debilitating lung infection in most cystic fibrosis patients. Adding to the significance of these infections is the fact that this organism is capable of rapidly developing resistance to many antibiotics, which significantly limits treatment options. While the need for novel antimicrobial treatments has been pressing for years, the development of useful new antibiotics has been difficult. One promising line of research has centered on the cell-to-cell signaling systems used by bacteria to control many functions, including virulence. P. aeruginosa uses three different intercellular signaling systems to coordinate gene expression and the topic of this proposal is the signal 2-heptyl-3-hydroxy-4-quinolone [referred to as the Pseudomonas Quinolone Signal (PQS)]. PQS is required for virulence in plants, insects, and animals and is produced in the lungs of cystic fibrosis patients who are infected by P. aeruginosa. Our plan is to complete experiments that will help us to better understand the significance of PQS in P. aeruginosa cell-to-cell signaling and virulence. We propose focused experiments that will address how PQS activates genes, and the mechanisms behind its synthesis. The long term goal of this research is to develop methods that interfere with PQS signaling. We believe that the PQS signaling system and the components required for its proper function will provide targets at which to aim future therapeutic interventions that will decrease P. aeruginosa virulence. [unreadable] [unreadable] [unreadable]